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The Journal of Neuroscience, April 27, 2005, 25(17):4375-4384; doi:10.1523/JNEUROSCI.0115-05.2005

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Behavioral/Systems/Cognitive
Identification of Glyoxalase-I as a Protein Marker in a Mouse Model of Extremes in Trait Anxiety

Simone A. Krömer, Melanie S. Keßler, Dale Milfay, Isabel N. Birg, Mirjam Bunck, Ludwig Czibere, Markus Panhuysen, Benno Pütz, Jan M. Deussing, Florian Holsboer, Rainer Landgraf, and Christoph W. Turck

Max-Planck Institute of Psychiatry, D-80804 Munich, Germany

For >15 generations, CD1 mice have been selectively and bidirectionally bred for either high-anxiety-related behavior (HAB-M) or low-anxiety-related behavior (LAB-M) on the elevated plus-maze. Independent of gender, HAB-M were more anxious than LAB-M animals in a variety of additional tests, including those reflecting risk assessment behaviors and ultrasound vocalization, with unselected CD1 "normal" control (NAB-M) and cross-mated (CM-M) mice displaying intermediate behavioral scores in most cases. Furthermore, in both the forced-swim and tail-suspension tests, LAB-M animals showed lower scores of immobility than did HAB-M and NAB-M animals, indicative of a reduced depression-like behavior. Using proteomic and microarray analyses, glyoxalase-I was identified as a protein marker, which is consistently expressed to a higher extent in LAB-M than in HAB-M mice in several brain areas. The same phenotype-dependent difference was found in red blood cells with NAB-M and CM-M animals showing intermediate expression profiles of glyoxalase-I. Additional studies will examine whether glyoxalase-I has an impact beyond that of a biomarker to predict the genetic predisposition to anxiety- and depression-like behavior.

Key words: anxiety; enzyme; biomarker; proteomics; HAB; depression; animal model; microarray

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Received Aug 6, 2004; revised March 8, 2005; accepted March 9, 2005.

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